Yale-New Haven Hospital

In neuronal dendrites of both rodents and flies, there are regularly spaced contact sites between the endoplasmic reticulum (ER) and plasma membrane, which function as hubs for regulating Ca 2+ homeostasis and facilitate long-range transmission of signals along the length of the dendrite. The ladder-like patterning of the neuronal ER and its plasma membrane junctions resembles that of the sarcoplasmic reticulum-plasma membrane junctions in muscles. SUMMARY Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at 1 mm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca 2+ channels and ER Ca 2+-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca 2+ homeostasis, and local activation of the Ca 2+ /calmodulin-dependent protein kinase II. Local spine stimulation activates the Ca 2+ modulatory machinery, facilitating signal transmission and ryanodine-receptor dependent Ca 2+ release at ER-PM junctions over 20 mm away. Thus, interconnected ER-PM junctions support signal propagation and Ca 2+ release from the spine-adjacent ER. The capacity of this subcellular architecture to modify both local and distant membrane-proximal biochemistry potentially contributes to dendritic computations.

OBJECTIVES This study investigates the differences between in-person versus virtual format of an advanced communication skills OSCE through thematic analyses of post-OSCE debrief transcripts. METHODS Two cohorts of senior medical students participated in either a 2019 in-person or 2021 virtual advanced communication skills OSCE. Students were grouped in triads and rotated through three of five possible cases. Afterwards, students participated in a faculty-led debrief (in-person in 2019, virtual in 2021). Inductive thematic analysis was used to compare the themes and the ratio of comments related to the themes were compared between the virtual and in-person OSCEs. RESULTS Thematic analyses for both in-person and virtual OSCEs identified the same four major themes (Case Review, Emotional Response, Feedback, and Reflection) and 11 subthemes. However, the ratio of comments related to Case Review was lower in the virtual OSCE compared to in-person (P < .0001). Analysis of subthemes within Case Review revealed the percentage of comments was higher for Content and lower for Challenges in the virtual OSCE compared to in-person (both P < .0001). There were no differences in the ratios of comments related to Emotional Response, Feedback, and Reflection, or their subthemes. CONCLUSION A virtual advanced communications skills OSCE for medical students showed identical qualitative themes to that from a prior in-person OSCE. However, students in the virtual OSCE focused more on matter-of-fact discussions about case content and less about the challenges they experienced. The findings suggest that some medical students may struggle with experiential learning in the virtual format, and have difficulty accessing or practicing their reflective observation skills based on Kolb's learning theory. Differences may be attributable to the additional cognitive load in the virtual setting, inadequate structural safeguards, and/or other limitations of virtual communication.

Introduction Intimate partner violence (IPV) is an important determinant of poor sexual and reproductive health. One’s sense of sexual autonomy may be an important concept in the context of IPV and sexual and reproductive health outcomes. Compromised sexual autonomy may explain the risk of poor sexual and reproductive health among individuals who experienced IPV; yet few studies have examined the role of sexual autonomy. The current study examined the mediating effects of sexual autonomy on the association between recent IPV, sexual risk and HIV-related worry. Methods One hundred ninety-eight sexually active women and men involved in past-year romantic partnerships completed an online survey in 2016. Path analysis was used to test the direct and indirect effects of sexual autonomy. Results Recent IPV predicted lower sexual autonomy (B = − .29, SE = .15, p < .05), unwanted condomless sex (aOR = 3.38, 95% CI 1.63–7.02), coercive sexual risk (aOR = 25.91, 95% CI 5.02–133.75), and HIV-related worry (aOR = 5.44, 95% CI 1.44–20.57). Lower sexual autonomy predicted unwanted condomless sex (aOR = .98, 95% CI .96–.99), coercive sexual risk (aOR = .95, 95% CI .90–.99), and HIV-related worry (aOR = .92, 95% CI .90–.97). Sexual autonomy mediated the association between IPV and HIV-related worry (indirect effect OR = 1.39, 95% CI 1.01–3.63). Conclusions Recent IPV experiences can weaken one’s sexual autonomy, which in turn creates concerns about acquiring HIV. HIV prevention programming should address the implications of IPV, promote sexual safety strategies, and develop tailored support to increase sexual autonomy among individuals navigating violence. Policy Implications Findings can inform the integration of trauma-informed policies and IPV screening practices in comprehensive sexual health programmatic initiatives.

Background While LRRK2 and GBA1 variants are associated with Parkinson's disease (PD), most carriers will not develop the disease. Objective To test if polygenic risk score (PRS) modifies disease risk and phenotypes in LRRK2 G2019S carriers, GBA1 carriers, and non-carriers (NC). Methods We genotyped 786 participants using Illumina's NeuroBooster-array (NBA) and sequenced the genome of 244, all of Ashkenazi ancestry (AJ), and calculated PRS to test its effects on clinically- and biologically-defined disease risk and phenotypes (n = 715). Among LRRK2 G2019S PD, we tested PRS association with α-synuclein seed-amplification-assay (n = 11). We used the PPMI and AMP-PD databases as validation cohorts. Results In clinically-defined PD, PRS significantly modified disease risk in GBA1 carriers and in NC ( p = 0.033 and p < 0.0001, respectively), and demonstrated a trend in LRRK2 G2019S carriers ( p = 0.054), with similar effect sizes (OR = 1.55, 1.62, and 1.49, respectively). PRS association with PD risk in LRRK2 was primarily driven by the rs7938782-A risk allele, replicated in AMP-PD (268 AJs LRRK2 G2019S carriers). PRS and age-at-onset were negatively correlated in NC ( p < 0.0001). NBA GBA1 genotype calls failed at GBA1 L483P and c.115 + 1G > A mutations. False negative call rate of 10.2% was observed for the imputed GBA1 N409S carriers. Conclusions PRS contributes to PD risk across different genotypes. The genetic and epigenetic role of rs7938782 in LRRK2 PD risk should be further explored. Future PRS models should be tailored to specific genotypes to better understand penetrance and phenotypes. Furthermore, models predicting PD defined biologically rather than clinically may further identify genetic risk factors for synucleinopathies.

Background Patients admitted with acute decompensated heart failure (ADHF) are vulnerable to declines in kidney function, but the exact mechanisms are unknown. Two novel hemodynamic markers, pulmonary artery pulsatility index (PAPI) and aortic pulsatility index (API) represent composite right and left-ventricular function respectively. Methods Consecutive unique patient admissions for ADHF to a single quaternary medical center with placement of a pulmonary artery (PA) catheter between 2015-2021 were reviewed. Cubic and linear regression models were used to examine the association between these markers with baseline estimated glomerular filtration rate (eGFR) and in-hospital eGFR slope. Multivariable Cox proportional hazards models were used to examine the association between PAPI and API with the need for dialysis via linkage of a national database. Covariates included demographics, comorbid conditions, home medications and baseline eGFR. Results The cohort included N = 753 patients with mean (SD) age 62.2 (14.4), eGFR 58.0 (27.1) ml/min/1.73m ² . For every halving of PAPI, there was a 3.3 (95% CI 1.5, 5.1) ml/min/1.73 m ² lower baseline eGFR, and a 0.78 (95% CI 0.32, 1.25) ml/min/1.73 m ² /week lower in-hospital eGFR slope. Over a median follow-up time of 30.3 months, lower PAPI was associated with higher hazard of dialysis during the follow-up period (HR 1.44 (95%CI 1.06, 1.96) per halving). There was no association between API with baseline eGFR, in-hospital eGFR slope, or dialysis. Conclusions Lower PAPI was associated with a lower baseline eGFR, lower in-hospital eGFR slope and higher risk of dialysis. API was not associated with any kidney outcomes.

This cross-sectional study evaluates the quality and accuracy of information presented on websites that sell compounded glucagon-like peptide-1 receptor agonists.

Importance Opioid use disorder (OUD) impacts millions of people worldwide. Prior studies investigating its underpinning neural mechanisms have not often considered how brain signals evolve over time, so it remains unclear whether brain dynamics are altered in OUD and have subsequent behavioral implications. Objective To characterize brain dynamic alterations and their association with cognitive control in individuals with OUD. Design, Setting, and Participants This case-control study collected functional magnetic resonance imaging (fMRI) data from individuals with OUD and healthy control (HC) participants. The study was performed at an academic research center and an outpatient clinic from August 2019 to May 2024. Exposure Individuals with OUD were all recently stabilized on medications for OUD (<24 weeks). Main Outcomes and Measures Recurring brain states supporting different cognitive processes were first identified in an independent sample with 390 participants. A multivariate computational framework extended these brain states to the current dataset to assess their moment-to-moment engagement within each individual. Resting-state and naturalistic fMRI investigated whether brain dynamic alterations were consistently observed in OUD. Using a drug cue paradigm in participants with OUD, the association between cognitive control and brain dynamics during exposure to opioid-related information was studied. Variations in continuous brain state engagement (ie, state engagement variability [SEV]) were extracted during resting-state, naturalistic, and drug-cue paradigms. Stroop assessed cognitive control. Results Overall, 99 HC participants (54 [54.5%] female; mean [SD] age, 31.71 [12.16] years) and 76 individuals with OUD (31 [40.8%] female; mean [SD] age, 39.37 [10.47] years) were included. Compared with HC participants, individuals with OUD demonstrated consistent SEV alterations during resting-state (99 HC participants; 71 individuals with OUD; F 4,161 = 6.83; P < .001) and naturalistic (96 HC participants; 76 individuals with OUD; F 4,163 = 9.93; P < .001) fMRI. Decreased cognitive control was associated with lower SEV during the rest period of a drug cue paradigm among 70 participants with OUD. For example, lower incongruent accuracy scores were associated with decreased transition SEV (ρ 58 = 0.34; P = .008). Conclusions and Relevance In this case-control study of brain dynamics in OUD, individuals with OUD experienced greater difficulty in effectively engaging various brain states to meet changing demands. Decreased cognitive control during the rest period of a drug cue paradigm suggests that these individuals had an impaired ability to disengage from opioid-related information. The current study introduces novel information that may serve as groundwork to strengthen cognitive control and reduce opioid-related preoccupation in OUD.

BACKGROUND Simultaneous symmetrizing surgery at the time of unilateral free flap reconstruction has been described as a method to facilitate single stage breast reconstruction. However, the impact on cost and number of additional procedures is not well described. METHODS Patients with unilateral free flap reconstruction were identified in national administrative data from 2017-2021 and followed for one year. Patients were stratified by immediate and delayed reconstruction, then further stratified into groups with simultaneous symmetrizing surgery and without simultaneous symmetrizing surgery. Thirty-day complications included transfusion, wound dehiscence, surgical site infection, hematoma/seroma and thromboembolism. Costs of initial hospitalization and subsequent surgeries were determined. Deferred symmetrizing surgeries within one year were identified. Chi-squared and Fisher exact tests, and Wilcoxon tests were used for statistical analysis. RESULTS A total of 1136 patients were identified. 638 were delayed reconstructions: 75 with simultaneous symmetrizing surgery and 563 without. There were no significant differences in patient characteristics or 30-day complications. Within one year of index reconstruction, fewer patients with simultaneous symmetrizing surgery underwent a revision surgery (29% vs 51%, (p=0.001)) or at least one additional procedure (36% vs 57%, p<0.001). Patients with simultaneous symmetrizing surgery had lower total costs ($35,897 vs$50,521, p=0.005). There were 498 immediate reconstructions: 63 with simultaneous symmetrizing surgery and 435 without. There were no significant differences in patient characteristics, 30-day complications, subsequent surgeries or total costs. CONCLUSION Symmetrizing procedures at the time of unilateral reconstruction may decrease cost and number of subsequent surgeries without increasing complications.

Family caregivers of patients with severe acute brain injury (SABI) are at risk for clinically significant chronic emotional distress, including depression, anxiety, and posttraumatic stress. Existing psychosocial interventions for caregivers of intensive care unit (ICU) patients are not tailored to the unique needs of caregivers of patients with SABI, do not demonstrate long-term efficacy, and may increase caregiver burden. In this study, we explored the needs and preferences for psychosocial services among SABI caregivers to inform the development and adaptation of interventions to reduce their emotional distress during and after their relative’s ICU admission. In this multicenter longitudinal qualitative study, we conducted semistructed interviews with SABI caregivers at two time points: during their relative’s ICU admission (n = 30) and 2 months later (n = 20). We analyzed qualitative data using a hybrid of inductive and deductive analytic techniques. We recruited family caregivers of patients with SABI from 14 US neuroscience ICUs. We conducted interviews over live video. Our convenience sample of SABI caregivers (n = 30) was recruited through referral by medical teams and nursing staffs across participating neuroscience ICUs. Caregivers included spouses, children, parents, and siblings to patients with SABI. We identified themes and subthemes related to participants’ preferences for (1) the content of psychosocial support services and (2) the delivery and implementation of psychosocial support services. Findings revealed an unmet need for psychosocial support around the time of ICU discharge and 2 months later, including information to understand their loved one’s condition and guide difficult decision-making, education regarding how best to communicate with the patient’s care team and other family members, and emotional and behavioral coping skills. Our findings provide specific recommendations to justify and inform the development and adaptation of psychosocial support services for SABI caregivers for delivery in the ICU and after discharge.

The sacrum can harbor a diverse group of both benign and malignant tumors, including metastases. Primary tumors of the sacrum can arise from bone, cartilage, marrow, notochordal remnants, or surrounding nerves and vessels. Among a variety of primary tumors of the spine, chordoma, germ cell tumors and Ewing’s sarcoma are recognized for their propensity to occur in the sacrum. Imaging is essential in diagnosis, pretreatment evaluation, and assessment of response to treatment. Radiography, CT and MRI are the primary modalities in assessing morphology and tumor extent whereas PET/CT is crucial in the evaluation of systemic disease in the setting of myeloma, lymphoproliferative disease, and metastasis. A definitive diagnosis is not always achievable by imaging as some tumors lack specific imaging features. However, as we detail in this comprehensive review, many entities have characteristic clinical and epidemiological factors as well as typical imaging findings that can help make either a confident diagnosis or offer a narrow list of differentials. We discuss a wide range of benign and malignant, primary, and secondary tumors that can involve the sacrum, highlighting the pertinent clinical details and typical imaging findings of these entities, enabling the reader to develop and apply a systematic approach to evaluating sacral masses on imaging. We also briefly describe non-neoplastic tumor mimics, which include developmental entities, infections, and insufficiency fractures.

In the last decades, research from cognitive science, clinical psychology, psychiatry, and social neuroscience has provided mounting evidence that several social cognitive abilities are impaired in people with schizophrenia and contribute to functional difficulties and poor clinical outcomes. Social dysfunction is a hallmark of the illness, and yet, social cognition is seldom assessed in clinical practice or targeted for treatment. In this article, 17 international experts, from three different continents and six countries with expertise in social cognition and social neuroscience in schizophrenia, convened several meetings to provide clinicians with a summary of the most recent international research on social cognition evaluation and treatment in schizophrenia, and to lay out primary recommendations and procedures that can be integrated into their practice. Given that many extant measures used to assess social cognition have been developed in North America or Western Europe, this article is also a call for researchers and clinicians to validate instruments internationally and we provide preliminary guidance for the adaptation and use of social cognitive measures in clinical and research evaluations internationally. This effort will assist promoting scientific rigor, enhanced clinical practice, and will help propel international scientific research and collaboration and patient care.

Context: A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis. Objective: The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis. Methods: This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022. The primary outcome was the proportion of patient-quarter observations with ODT use stratified by age, sex, fragility fracture, and documented osteoporosis. Cuzick tests were performed to assess trends ODT use. Results: Analysis of 166 673 420 patient-quarter observations revealed that over 70% of patients with fragility fractures did not have documented osteoporosis. Among women aged ≥65 years with documented osteoporosis, ODT fill rates increased between 2011 and 2022 from 36.3% to 50.1% for women without fragility fractures (P < .001) and from 30.8% to 43.7% for women with fragility fractures (P < .001). However, ODT fill rates declined (9.2% to 7.4% between 2011 and 2022) for women with fragility fractures and no documented osteoporosis (P = .015). Similar trends were observed among women aged 50-64 years and men. Conclusion: ODT use for patients with documented osteoporosis has increased but remains low. Low rates of ODT use for patients with fragility fractures in the absence of documented osteoporosis suggests that underdiagnosis of osteoporosis contributes to underuse of ODTs.

The ventrolateral pallial (VLp) excitatory neurons in the claustro-amygdalar complex and piriform cortex (PIR; which forms part of the palaeocortex) form reciprocal connections with the prefrontal cortex (PFC), integrating cognitive and sensory information that results in adaptive behaviours1, 2, 3, 4–5. Early-life disruptions in these circuits are linked to neuropsychiatric disorders4, 5, 6, 7–8, highlighting the importance of understanding their development. Here we reveal that the transcription factors SOX4, SOX11 and TFAP2D have a pivotal role in the development, identity and PFC connectivity of these excitatory neurons. The absence of SOX4 and SOX11 in post-mitotic excitatory neurons results in a marked reduction in the size of the basolateral amygdala complex (BLC), claustrum (CLA) and PIR. These transcription factors control BLC formation through direct regulation of Tfap2d expression. Cross-species analyses, including in humans, identified conserved Tfap2d expression in developing excitatory neurons of BLC, CLA, PIR and the associated transitional areas of the frontal, insular and temporal cortex. Although the loss and haploinsufficiency of Tfap2d yield similar alterations in learned threat-response behaviours, differences emerge in the phenotypes at different Tfap2d dosages, particularly in terms of changes observed in BLC size and BLC–PFC connectivity. This underscores the importance of Tfap2d dosage in orchestrating developmental shifts in BLC–PFC connectivity and behavioural modifications that resemble symptoms of neuropsychiatric disorders. Together, these findings reveal key elements of a conserved gene regulatory network that shapes the development and function of crucial VLp excitatory neurons and their PFC connectivity and offer insights into their evolution and alterations in neuropsychiatric disorders.

Medical facilities are civilian objects specially protected by international humanitarian law. Despite the need for systematic documentation of the effects of war on medical facilities for judiciary accountability, current methods for surveilling damage to protected civilian objects during ongoing armed conflict are insufficient. Satellite imagery damage assessment confers significant possibilities for investigating patterns of war. We leveraged commercially and publicly available satellite imagery and cross-referenced geolocated facility data to conduct a pre-post quasi-experimental study of damage to medical facilities in Mariupol, Ukraine as a result of Russia’s invasion. We found that 77% of medical facilities in Mariupol sustained damage during Russia’s siege lasting from February 24—May 20, 2022. Facility size was not associated with damage, suggesting that attacks on medical facilities are not random but instead may have been the result of intentional targeting. This is the first cross-referenced pre-post census study of the effects of an ongoing conflict on specially protected medical infrastructure.

Purpose of Review Significant inequities persist in hypertension detection and control, with minoritized populations disproportionately experiencing organ damage and premature death due to uncontrolled hypertension. Remote blood pressure monitoring combined with telehealth visits (RBPM) is proving to be an effective strategy for controlling hypertension. Yet there are challenges related to technology adoption, patient engagement and social determinants of health (SDoH), contributing to disparities in patient outcomes. This review summarizes the evidence to date for RBPM, focusing on the potential to advance health equity in blood pressure control and the existing levers for largescale implementation. Recent Findings Several studies demonstrate the promise of RBPM programs to address health disparities through: (1) the use of cellular-enabled blood pressure machines that do not require internet access or smart devices to connect readings into the medical record; (2) emphasis on home blood pressure monitoring to illuminate the daily factors that influence blood pressure control, thereby increasing patient empowerment; (3) adoption of standardized algorithms for hypertension management; and (4) integration of services to address SDoH. Multidisciplinary, non-physician care teams that include nurses, pharmacists, and community health workers are integral to this model. However, most studies have not embraced all aspects of RBPM, and implementation is challenging as current payment models do not support the digital components of RBPM or a diverse workforce of hypertension providers. Conclusion To address hypertension disparities, RBPM programs need to integrate digital technology that is accessible to all users as well as multidisciplinary care teams that attend to the medical and social needs of populations experiencing health inequities.

Objectives: To analyze sex differences in outcomes in Tourette syndrome (TS) and Persistent Motor or Vocal tic disorders (PMVT) in the Tourette Association of America International Consortium for Genetics (TAAICG) dataset. Methods: The relationship between sex and clinical measures was explored in 2,403 participants (N = 2,109 with TS; N = 294 with PMVT) from the TAAICG dataset using generalized estimating equation regression models, and adjusted for age and family relationships. Results: Female (vs male) participants with TS (25.5% of the sample) had 0.46 times lower odds of being formally diagnosed clinically with TS before the research study (p < 0.00001), later age at symptom onset (6.5 ± 2.8 vs 6.0 ± 2.7; p = 0.001), later age at diagnosis (13.3 ± 11.2 vs 10.7 ± 8.1; p = 0.0001), a longer time-to-diagnosis (3 [1, 7] vs 2 [1, 5], p = 0.01), and lower tic severity (28.4 ± 9.1 vs 30.7 ± 8.7); p < 0.0001). Female (vs male) participants with PMVT (42.9% of the sample) had an earlier age at symptom onset (7.9 ± 3.3 vs 8.9 ± 3.7; p = 0.05). Discussion: Female (vs male) participants with TS are less likely to be formally diagnosed, have later age at symptom onset, later age at diagnosis, and longer time-to-diagnosis. Female (vs male) participants with PMVT have an earlier age at symptom onset. Future research is needed to understand differences longitudinally in TS and PMVT.

Surveillance of individuals at high‐risk of pancreatic cancer using CAPS criteria and other expert consensus guidelines may result in earlier pancreatic cancer detection in some cases; therefore, clinicians are responsible for appropriately identifying and referring these individuals to appropriate high‐risk pancreas cancer screening programs. This study aimed at assessing the perspective, knowledge, and clinical practices of cancer genetic counselors surveyed nationwide towards identification of individuals at high‐risk of pancreatic cancer and utilization of high‐risk pancreatic cancer screening programs. One hundred and eighty‐nine genetic counselors who listed “Cancer” as their specialty on the NSGC website responded to the survey, which consisted of multiple practice‐based, knowledge‐based, and clinical vignette‐based questions. Almost 70% of the genetic counselors surveyed accurately identified when an individual would be considered for high‐risk pancreatic cancer screening, when using 2019 CAPS consensus guidelines as a benchmark. Access to high‐risk pancreatic cancer screening programs and increased provider comfort in counseling individuals at high‐risk of pancreatic cancer were found to be statistically associated in accurate identification of high‐risk individuals in three of the clinical vignettes. Additionally, 60% of genetic counselors reported the majority of high‐risk individuals accept a referral for pancreatic cancer screening, which shows a high uptake of patients accepting referrals from genetic counselors. Genetic counselors have high accuracy in determining who is eligible for high‐risk pancreas screening; thus, they are the ideal providers for initiating referrals to high‐risk pancreatic cancer screening programs. Genetic counseling programs and high‐risk pancreatic cancer screening programs should establish a close working relationship to optimize the identification and subsequent referrals of high‐risk individuals eligible for pancreas cancer screening.

Background/aims: Randomized clinical trials often use stratification to ensure balance between arms. Analysis of primary endpoints of these trials typically uses a "stratified analysis," in which analyses are performed separately in each subgroup defined by the stratification factors, and those separate analyses are weighted and combined. In the phase 3 setting, stratified analyses based on a small number of stratification factors can provide a small increase in power. The impact on power and type-1 error of stratification in the setting of smaller sample sizes as in randomized phase 2 trials has not been well characterized. Methods: We performed computational studies to characterize the power and cross-arm balance of modestly sized clinical trials (less than 170 patients) with varying numbers of stratification factors (0-6), sample sizes, randomization ratios (1:1 vs 2:1), and randomization methods (dynamic balancing vs stratified block). Results: We found that the power of unstratified analyses was minimally impacted by the number of stratification factors used in randomization. Analyses stratified by 1-3 factors maintained power over 80%, while power dropped below 80% when four or more stratification factors were used. These trends held regardless of sample size, randomization ratio, and randomization method. For a given randomization ratio and sample size, increasing the number of factors used in randomization had an adverse impact on cross-arm balance. Stratified block randomization performed worse than dynamic balancing with respect to cross-arm balance when three or more stratification factors were used. Conclusion: Stratified analyses can decrease power in the setting of phase 2 trials when the number of patients in a stratification subgroup is small.